Mandibular bone defect healing using polylactic acid-nano-hydroxyapatite-gelatin scaffold loaded with hesperidin and dental pulp stem cells in rat

Arya Khosronejad; Hamidreza Arabion; Aida Iraji; Mohamad Mokhtarzadegan; Seyyed Sajad Daneshi; Seyedeh-Leili Asadi-Yousefabad; Shahrokh Zare; Fariborz Nowzari; Shekofeh Abbaspour; Fatemeh Akbarizadeh; Ehsan Aliabadi; Mohammad Amin Amiri; Moein Zarei; Reyhaneh Ebrahimi; Nadiar M Mussin; Madina A Kurmanalina; Nader Tanideh; Amin Tamadon

doi:10.1016/j.tice.2024.102700

Mandibular bone defect healing using polylactic acid-nano-hydroxyapatite-gelatin scaffold loaded with hesperidin and dental pulp stem cells in rat

Tissue Cell. 2024 Dec 24:93:102700. doi: 10.1016/j.tice.2024.102700. Online ahead of print.

Authors

Arya Khosronejad¹, Hamidreza Arabion², Aida Iraji³, Mohamad Mokhtarzadegan⁴, Seyyed Sajad Daneshi⁵, Seyedeh-Leili Asadi-Yousefabad⁵, Shahrokh Zare⁵, Fariborz Nowzari⁵, Shekofeh Abbaspour⁶, Fatemeh Akbarizadeh⁷, Ehsan Aliabadi⁸, Mohammad Amin Amiri⁹, Moein Zarei¹⁰, Reyhaneh Ebrahimi¹¹, Nadiar M Mussin¹², Madina A Kurmanalina¹³, Nader Tanideh¹⁴, Amin Tamadon¹⁵

Affiliations

¹ Department of Oral and Maxillofacial Surgery, School of Dentistry, Shiraz University of Medical Science, Shiraz, Iran.
² Department of Oral and Maxillofacial Surgery, School of Dentistry, Shiraz University of Medical Science, Shiraz, Iran. Electronic address: arabiun@sums.ac.ir.
³ Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Central Research laboratory, Shiraz University of Medical Sciences, Shiraz, Iran.
⁴ School of Metallurgy and Materials Engineering, College of Engineering, University of Tehran, Tehran, Iran. Electronic address: m.mokhtarzadegan@ut.ac.ir.
⁵ Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
⁶ Department of Chemical and Polymer Engineering, Faculty of Engineering, Yazd University, Yazd, Iran.
⁷ Department of Oral & Maxillofacial Radiology, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: f_akbarizadeh@sums.ac.ir.
⁸ Department of Oral and Maxillofacial Surgery, School of Dentistry, Shiraz University of Medical Science, Shiraz, Iran. Electronic address: aliabadie@sums.ac.ir.
⁹ School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.
¹⁰ Department of Polymer and Biomaterials Science, Faculty of Chemical Technology and Engineering, West Pomeranian University of Technology, Szczecin, Al. Piastow 45, Szczecin 71-311, Poland. Electronic address: zm47832@zut.edu.pl.
¹¹ Department of Periodontics, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.
¹² Department of Surgery No. 2, West Kazakhstan Medical University, Aktobe, Kazakhstan. Electronic address: nadiar_musin@zkmu.kz.
¹³ Department of Therapeutic and Prosthetic Dentistry, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan.
¹⁴ Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: tanidehn@gmail.com.
¹⁵ Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Natural Sciences, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan. Electronic address: amintamaddon@yahoo.com.

PMID: 39724839
DOI: 10.1016/j.tice.2024.102700

Abstract

Addressing mandibular defects poses a significant challenge in maxillofacial surgery. Recent advancements have led to the development of various biomimetic composite scaffolds aimed at facilitating mandibular defect reconstruction. This study aimed to assess the regenerative potential of a novel composite scaffold consisting of polylactic acid (PLA), hydroxyapatite nanoparticles (n-HA), gelatin, hesperidin, and human dental pulp stem cells (DPSCs) in a rat model of mandibular bone defect. The PLA-HA-GLA composite was synthesized using solvent casting-leaching and freeze-drying methods and subsequently treated with 11 mg of hesperidin. The physicochemical properties of the PLA-HA-GLA and PLA-HA-GLA-HIS composites were analyzed by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and thermal gravimetric analysis (TGA). Additionally, the mechanical properties and cytotoxicity of DPSCs were assessed. Subsequently, PLA-HA-GLA and PLA-HA-GLA-HIS scaffolds with or without DPSCs were implanted into mandibular bone defects in rats, followed by histopathological, histomorphometric, and cone-beam computed tomography (CBCT) evaluations after eight weeks. SEM analysis revealed the porous structure of the fabricated PLA-HA-GLA and PLA-HA-GLA-HIS composites without aggregation. FTIR and XRD analyses confirmed the presence of functional groups and elements associated with PLA, HA, GLA, and hesperidin in the composites. Although the PLA-HA-GLA-HIS composite exhibited good thermal stability, its mechanical properties decreased after the addition of hesperidin. The cell viability of DPSCs on the surface of the PLA-HA-GLA-HIS scaffolds was statistically significant compared to that of the control group. Furthermore, histopathological, histomorphometric, and radiological evaluations demonstrated that the implantation of the DPSC-loaded PLA-HA-GLA-HIS scaffold had a beneficial effect on bone tissue reconstruction in rats with mandibular defects. These findings highlight the potential of DPSC-loaded PLA-HA-GLA-HIS composite scaffolds for spongy bone tissue engineering and mandibular defect repair.

Keywords: Dental pulp stem cells; Gelatin; Hesperidin; Mandibular defect; Nano-hydroxyapatite; Poly-lactic acid; Rats; Tissue scaffold.